High-Throughput Microfluidic Enrichment of Rare Cells from Large Volumes of Blood

Abstract
Deterministic lateral displacement (DLD) arrays are microfluidic devices capable of high-resolution separation of particles based on size. DLD arrays have been applied to separation of large cells from blood for a wide variety of diagnostic and analytical purposes. The volume of blood processed in these applications has been limited by volume-dependent performance degradation and throughput (volume/time) limitations. We address these issues in three ways in this thesis. First, we develop fabrication methods that increase the density of DLD arrays on a chip of a given area, resulting in an increase in the volumetric flow rate for a given pressure by a factor of ten. Second, we identify conventional platelet-driven clot formation as the source of the volume-dependent performance degradation and develop a method to completely inhibit clot formation in the DLD array, resulting in a 1000-fold increase in the volume of blood processed without device performance degradation. Third, we characterize the effect of post shape on the behavior of cells at high flow rates by showing how post shape can be used to minimize shear-induced compression that reduces the target cell yield and to minimize hydrodynamic asymmetry that results in undesirable displacement of erythrocytes. Together, these three advances will enable high-yield separation of rare cells from more than 100 mL of blood in less than 1 hour using DLD arrays.